Dipyrromethanes are compounds known for more than a century (Baeyer, A., Ber. Dtsch. Chem. Ges. 1886, 19, 2184). Dipyrromethanes were substituted (U.S. Pat. Nos. 6,924,375, and 5,599,948) and used as intermediates for the synthesis of calixpyrroles, porphyrines (U.S. Pat. Nos. 7,501,507, 7,323,561, 7,148,361 and 5,767,272; WO 03/027066 A2 (Apr. 3, 2003); and EP 0 665 230 A2 (Aug. 2, 1995)) and expanded porphyrines (U.S. Pat. No. 5,512,675). However, only recently a reliable synthetic method for their preparation was reported (U.S. Pat. No. 7,022,862); and Litter, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O'Shea, D. F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391-1396).
In U.S. Pat. No. 7,022,862, Lindsey et al. describe a process for the preparation of dipyrromethanes wherein pyrrole derivative is coupled with an appropriate carbonyl derivative in the presence of acid. In the '862 patent, the carbonyl derivative is comprised of aromatic and aliphatic aldehydes and ketones, but not adamantane derivatives, the subject of this invention. In addition, the use of dipyrromethanes as anion binding reagents and intermediates for anion sensors is not described by the '862 patent. Only Kar and Lightner describe a compound in which the adamantane moiety is attached to dipyrromethane (Heterocycl. Chem. 1998, 35, 795-803). The described adamantane-dipyrromethane is a bilivedrin derivative, but its use for binding anions has not been reported.
Adamantane derivatives are characterized by lipophilicity which ensures the solubility of adamantane-dipyrromethanes in organic solvents and provides the applicability of adamantane-dipyrromethanes as anion extracting agents. Anions play a key role in chemical and biological processes. Many anions act as nucleophiles, bases, redox agents or phase transfer catalysts, while most enzymes bind anions as either substrates or cofactors. Additionally, it is of great importance to detect anionic pollutants, such as phosphates and nitrates in ground water. Consequently, it is highly desirable to obtain new anion sensors which would be characterized by higher binding constants and selectivity. This demand has inspired research during the last 20 years which has resulted in numerous publications (e.g. Chem. Rev. 1997, 97, 1515-1566; Angew. Chem. Int. Ed. 2001, 40, 486-516; Coord. Chem. Rev. 2003, 240, issues 1-2; Chem. Rev. 2003, 103, 4419-4476; Top. Curr. Chem. 2005, 255; Chemm. Commun., 2005, 3761-3772; Tetrahedron, 2005, 61, 8551-8588; Acc. Chem. Res. 2006, 39, 343-353; and Acc. Chem. Res. 2006, 39, 465-475). A significant number of molecules which are used as anion sensors are composed of pyrrole subunits. Namely, pyrrole has an acidic NH proton to which anion can be attached by hydrogen bonds. Among these molecules, anion sensing has been reported for the derivatives of amidopyrroles, calix-pyrroles, sapphyrines and porphyrines, as well as dipyrroquinoxalines.
In all the mentioned molecules, binding of the anion is accomplished by the presence of two or more NH-anion hydrogen bonds. The presence of two NH protons is sufficient to accomplish binding of an anion with sufficient binding constants (as in the case of dipyrroquinoxalines), thus prompting investigation of the applicability of dipyrromethanes as anion sensors.